Gene delivery vehicles in the treatment of neurodegenerative diseases

Abstract

Currently no therapies that provide either protection or restoration of neuronal function for adult onset neurodegenerative diseases such as Parkinson's disease exist. Many clinical efforts to provide such benefits by infusion of neurotropic factors have failed. An alternative approach such as viral construct transduction may be used to directly activate the intracellular signaling pathways that mediate neurotrophic effects and induce axon growth. Viral construct transduction of dopaminergic neurons with a constitutively active human form of the p70S6K gene—hp70S6K (CA)—was shown to induce axon regeneration from living dopaminergic cell bodies that had no living axons.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims the benefit of Provisional Application No. 61 / 702,184, filed Sep. 17, 2012, the entire contents of which are hereby incorporated by reference as if fully set forth herein, under 35 U.S.C. §119(e).STATEMENT OF GOVERNMENT INTEREST[0002]This invention was made with Government support under Grant Nos. NS026836 and NS038370, awarded by the National Institute of Health and Grant No. W81XWH-12-1-0051, awarded by the United States Army Medical Research and Material Command. The Government has certain rights in the invention.BACKGROUND[0003]Parkinson's disease (PD) is a major public health problem in the world, with an estimated 1,000,000 individuals affected in the United States alone. It is a chronic, progressive, neurodegenerative disease caused by the death of neurons that produce dopamine—dopaminergic neurons—a neurotransmitter essential for proper muscle coordination, movement, and balance in the substantia nig...

AI Technical Summary

Problems solved by technology

Parkinson's disease (PD) is a major public health problem in the world, with an estimated 1,000,000 individuals affected in the United States alone.

However, chronic pharmacological treatment with the dopamine precursor L-Dopa leads to a display of involuntary abnormal movements called dyskinesias in PD patients and often cognitive impairment.

And there is no treatment that prevents deterioration attributable to progressive neurodegeneration.

Other approaches involve infusing a protein molecule into the brain but off target effects occur that are unacceptable rendering therapeutic interventions that block or slow down the ongoing degenerative process less than successful.

Currently, no therapies exist that provide either protection or restoration of neuronal function for adult onset neurodegenerative diseases such as PD.

Many clinical efforts to provide such benefits by infusion of neurotrophic factors have failed, in spite of robust effects in preclinical assessments.

One important reason for these failures is the difficulty, due to diffusion limits, of providing these protein molecules in sufficient amounts to the intended cellular targets in the central nervous system.

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